We plan to continue our studies of epithelial liver cells isolated from rats and established in vitro after administration of diethylnitrosamine in the drinking water. Transformed cells have been cloned which show heritable, stably maintained cytoplasmic abnormalities (Mallory hyalin bodies) and others that do not. These will be further examined and compared. The relationship of cytoskeletal alterations to oncogenesis and the possible involvement of a mutational event will be investigated. Cell-cell hybridization will be used to explore whether the appearance of the hyalin body can be associated with specific chromosomes. Mallory bodies will be purified and characterized by biochemical and immunochemical techniques. Liver specimens from patients with advanced alcoholic cirrhosis, known to contain large numbers of cells with Mallory bodies, will be cultured in vitro and in nude mice and the lesion will be compared with those induced by carcinogens in the rat. Normal liver cells will be exposed in vitro to carcinogens or alcohol either alone or in combination with promoters, to study events in malignant transformation.